Effectiveness of Nasal Continuous Positive Airway Pressure vs Nasal Intermittent Positive Pressure Ventilation vs Noninvasive High-Frequency Oscillatory Ventilation as Support After Extubation of Neonates Born Extremely Preterm or With More Severe Respiratory Failure

Key Points Question Is nasal continuous positive airway pressure (NCPAP), nasal intermittent positive pressure ventilation (NIPPV), or noninvasive high-frequency oscillatory ventilation (NHFOV) more beneficial in reducing invasive mechanical ventilation (IMV) in neonates? Findings This secondary analysis of a randomized clinical trial involving 1137 neonates found that neonates receiving NIPPV or NHFOV had fewer reintubations (range, −28% to −15%), fewer early (within 48 hours after extubation) reintubations (range, −24% to −20%), and shorter duration of IMV (range, −5.0 to −2.3 days) than those supported with NCPAP. Meaning These results suggest that NIPPV and NHFOV are essentially similar, and better than NCPAP, in terms of reintubation and duration of IMV in extremely preterm neonates and those with more severe respiratory failure.


eFigure 1. CONSORT Flowchart of the Original NASONE Trial.
For the 80 neonates who met an exclusion criterion, the distribution was as follows: grade-IV IVH (n=21), major congenital anomalies/chromosomal abnormalities (n=9), upper respiratory tract abnormalities (n=11), need for surgery known before the first extubation (n=35), birth weight <600g (n=4). The allocated treatment was discontinued in 53 neonates because their parents/guardians withdrew their consent to participation in the trial.
Assessed for eligibility (n=1974) ) Excluded (n=481) ¨ Met at least one exclusion criterion (n=80) ¨ Parental refuse to participate (n=315) ¨ Transfer to another hospital before randomization (n=86) Analysed ( Figure 1A in the text, for neonates of gestational age 28 or fewer weeks, P = .007 for noninvasive positive pressure ventilation (NIPPV) vs nasal continuous positive airway pressure (NCPAP), and P < .001 for noninvasive high-frequency oscillation ventilation (NHFOV) vs NCPAP. For neonates invasively ventilated for at least 1 week, P < .001 for NIPPV vs NCPAP and NHFOV vs NCPAP. For neonates with CO2 greater than 50 mm Hg before or in the 24 hours after extubation, P = .003 for NIPPV vs NCPAP, and P < .001 for NHFOV vs NCPAP. For Figure 1B in the text, for neonates of gestational age 28 or fewer weeks, P < .001 for NIPPV vs NCPAP and NHFOV vs NCPAP. For neonates invasively ventilated for at least 1 week, P < .001 for NIPPV vs NCPAP and NHFOV vs NCPAP. For neonates with CO2 greater than 50 mm Hg before or in the 24 hours after extubation, P < .001 for NIPPV vs NCPAP, and P = .01 for NHFOV vs NCPAP.
For Figure 2A in the text, for the mean difference in IMV duration in neonates of gestational age up to 28 weeks, P = .03 for noninvasive positive pressure ventilation (NIPPV) vs nasal continuous positive airway pressure (NCPAP), and P = .008 for noninvasive high-frequency oscillation ventilation (NHFOV) vs NCPAP. For the mean difference in IMV duration in neonates invasively ventilated for at least 1 week, P < .001 for NIPPV vs NCPAP and NHFOV vs NCPAP, and P = .03 for NIPPV vs NHFOV. For the mean difference in IMV duration in neonates with CO2 greater than 50 mm Hg before or in the 24 hours after extubation, P = .04 for NHFOV vs NCPAP. For Figure 2B in the text, for the mean difference in ventilator-free days for neonates with CO2 greater than 50 mm Hg before or in the 24 hours after extubation, P = .04 for NIPPV vs NCPAP.
For Figure 3A in the text, for the difference in risk of BPD in neonates of gestational age 28 or fewer weeks, P = .01 for noninvasive highfrequency oscillation ventilation (NHFOV) vs nasal continuous positive airway pressure (NCPAP). For Figure 3B in the text, for the difference in risk of moderate-to-severe BPD in neonates of gestational age 28 or fewer weeks, P = .04 for NHFOV vs NCPAP. For the difference in risk of moderate-to-severe BPD in neonates in neonates invasively ventilated for at least 1 week, P = .02 for NHFOV vs NCPAP. For the difference in risk of moderate-to-severe BPD in neonates with CO2 greater than 50 mm Hg before or in the 24 hours after extubation, P = .03 for NHFOV vs NCPAP.
For Figure 4A in the text, for the difference in oxygenation index for neonates of gestational age 28 or fewer weeks, P = .001 for noninvasive high-frequency oscillation ventilation (NHFOV) vs nasal continuous positive airway pressure (NCPAP), and P = .05 for noninvasive positive pressure ventilation (NIPPV) vs NHFOV. For the difference in oxygenation index for neonates invasively ventilated for at least 1 week, P = .04 for NHFOV vs NCPAP, and P = .007 for NIPPV vs NHFOV. For the difference in oxygenation index for neonates with CO2 greater than 50 mm Hg before or in the 24 hours after extubation, P = .005 for NHFOV vs NCPAP, and P = .04 for NIPPV vs NHFOV. For Figure 4B in the text, for the difference in CO2 for neonates of gestational age 28 or fewer weeks, P = .02 for NHFOV vs NCPAP. For the difference in CO2 for neonates invasively ventilated for at least 1 week, P = .04 for NIPPV vs NCPAP, and P = .02 for NHFOV vs NCPAP.

NCPAP -NIPPV NCPAP -NHFOV NIPPV -NHFOV Difference
Post 7 eTable 3. Interaction Analyses for All Coprimary Outcomes. Data are expressed as hazard ratio (for reintubation and early reintubations) or  coefficient (for duration of invasive ventilation and ventilator-free days) relative to the interaction term between the study intervention and the variable used to define subgroups, per each regression model. Abbreviations: CI: confidence interval; HR: hazard ratio; IMV: invasive mechanical ventilation; VFD: ventilator-free days.